Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “AL amyloidosis”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 19 recordsLinked to original sources
PubMed1995

[AL amyloidosis].

AL amyloidosis is one type of systemic amyloidosis. AL represents Amyloid of Light chains (of Ig's) type. Diagnosis of amyloid must be carried out by patho-histological Congo-red stains of the biopsied materials under suspicion of amyloid deposits from patients with various clinical manifestations, including macroglossia, cardiac abnormalities, ECG abnormalities, GI tract problems or carpal-tunnel syndrome. Al amyloidosis may be also termed as plasma cell dyscrasia (PCD) associated amyloidosis, or monoclonal gammopathy associated amyloidosis. As to classification, AL amyloidosis consists of primary (or idiopathic) amyloidosis, and myeloma-associated (and then macroglobulinemia-associated) amyloidosis. As similarly to myeloma, patients with AL amyloidosis have monoclonal Ig's in the serum and-or in the urine. Furthermore, there have been known to be a higher incidence of Bence Jones proteins as well as more lambda than kappa among patients with AL amyloidosis compared with distributions of monoclonal Ig's among myeloma patients. It is also important for clinicians to recognize a data of a median survival of 12 months (only 4 months if cardiac amyloid occurred) in all patients with AL amyloid VS, a data of a median survival of about 36 months in myeloma patients. An attempt to clarify a way to an early diagnosis of AL amyloidosis should be investigated.

Amyloidosis↗
PubMed2000

[Current treatment of AL amyloidosis].

AL amyloidosis is a plasma cell disorder characterized by the tissue accumulation of immunoglobulin light chains. The prognosis of AL amyloidosis is poor, with a median survival inferior to two years. Amyloid deposits, responsible for the clinical manifestations of this disease, can regress at least partially after the suppression of the production of amyloid precursors. Therefore, current treatment strategies in AL amyloidosis aim at reducing the plasma cell clones, using chemotherapy regimens applied in multiple myeloma. A combination of melphalan and prednisone is the standard therapy of AL amyloidosis, but its results remain disappointing. Intensive chemotherapy regimens, with high-dose melphalan followed by peripheral blood stem cell transplantation, lead to increased response rates and improved survival, but are complicated by severe short term morbidity and mortality. These regimens offer the best clinical perspectives for selected patients, until the introduction of innovative agents capable of interfering with amyloid fibril formation.

Amyloid↗
PubMed1987

Ptosis and dermatochalasis as presenting signs in a case of occult primary systemic amyloidosis (AL).

Amyloidosis (AL) is a disease characterized by the extracellular deposition of a complex glycoprotein, part of which is derived from light chains of immunoglobulins. The ocular adnexa can be involved in both systemic primary amyloidosis (AL), usually associated with multiple myeloma or other immunologic disorders, or in a localized form without such systemic implications. We present the case report of a 65-year-old man in whom occult primary systemic amyloidosis (AL), associated with a monoclonal IgG-kappa gammopathy, occurred with presenting signs of ptosis and dermatochalasis secondary to infiltration of the extraocular and orbicularis oculi muscles with amyloid.

Aged↗
PubMed2000

Analysis of plasma cell clonality in localized AL amyloidosis.

AL amyloidosis is characterized by fibrillar tissue deposits composed of monoclonal immunoglobulin light chains(IgLs). It has been speculated that clonal expansion of plasma cells may occur locally and produce amyloidogenic IgLs. Both immunohistochemistry and molecular genetics are useful for examining plasma cell clonality from paraffin-embedded tissue sections, which are easy to obtain. We evaluated plasma cell clonality in 16 biopsy cases of localized AL amyloidosis using these two methods. A clonal excess of plasma cells was detected in 6 (37.5%) cases immunohistochemically, in 10 (62.5%) cases molecularly, and in 13 (81.3%) cases by at least one of the two methods. These results support local synthesis of the light chain proteins in localized AL amyloidosis.

Adult↗
PubMed2001

[AL amyloidosis].

AL amyloidosis is a systemic disease caused by the deposition of fibrillar proteins in organs and tissues. These deposits are responsible for organic dysfunctions and may be rapidly lethal. Current therapy is unsatisfactory. We describe three clinical cases of multisystemic AL amyloidosis but with different initial presentation: nephrotic syndrome, cardiac failure and hepatic insufficiency. We review the literature about the clinical features, diagnostic methods and treatment of the disease.

Aged↗
PubMed1997

Allogeneic bone marrow transplantation for AL amyloidosis.

AL amyloidosis is an infiltrative disorder characterized by the extracellular deposition of insoluble fibrillar immunoglobulin light chains whose production results from a plasma cell dyscrasia. Treatment with melphalan has resulted in an improvement in a few patients. Recently, intensive chemotherapy followed by autologous or syngeneic stem cell support has been shown to offer potential benefit. Allogeneic stem cell support after intensive therapy would retain the benefits of autologous transplantation, with the additional advantages of a tumor-free graft and of a possible graft-versus-tumor effect. We report a patient with AL amyloidosis and significant proteinuria. She improved after an allogeneic bone marrow transplantation.

Amyloidosis↗
PubMed2003

Phenotypic analysis of plasma cells in bone marrow using flow cytometry in AL amyloidosis.

AL amyloidosis is an intractable disease resulting from a plasma cell dyscrasia which has a wide clinical spectrum. To investigate the phenotype of plasma cells in the bone marrow, a flow cytometric analysis was carried out in 10 patients with this disease (mean age, 57.8 +/- 7.9 years) and controls with M-protein (positive controls, n = 4) and without it (negative controls, n = 8). All patients were shown to have either A kappa- or A lambda-immunoreactive amyloid deposits on the biopsied tissues. On flow cytometry CD38++CD19+CD56- cells (polyclonal plasma cells) showed no significant difference between patients (0.59 +/- 0.37%) and either negative (2.25 +/- 2.84%) or positive controls (0.38 +/- 0.20%), while CD38++CD19-CD56+ cells (monoclonal plasma cells) showed a significantly higher level in the patients (1.34 +/- 1.54%) than in either negative (0.041 +/- 0.004%, p < 0.005) or positive controls (0.11 +/- 0.09%, p < 0.05). With respect to maturation of plasma cells, five of the patients (50%), three of the positive controls (75%) and all of the negative controls showed a dominant proliferation of mature subtype (CD45+MPC-1+CD49e- or CD45+MPC-1+CD49e+). Immature (CD45+MPC-1- or CD45-MPC-1-) and intermediate (CD45-MPC-1+CD49e-) subtypes were dominantly present in the bone marrow in 2 and 3 patients, respectively. In AL amyloidosis monoclonal plasma cells producing M-protein can be easily and reliably detected in the bone marrow by flow cytometry. This analysis might provide plasma cell phenotypic markers useful for assessing the prognosis and for monitoring the response to treatment.

ADP-ribosyl Cyclase↗
PubMed2002

Toxic megacolon: a life-threatening complication of high-dose therapy and autologous stem cell transplantation among patients with AL amyloidosis.

AL amyloidosis is a plasma cell disorder in which tissue deposition of immunoglobulin light chains leads to organ dysfunction. Recent reports of high-dose therapy with autologous stem cell transplantation for amyloidosis suggest higher response rates and extended survival compared to those seen with conventional chemotherapy. However, substantial treatment-related toxicity has been observed. This case series describes our institutional experience with autologous transplantation in four patients with amyloidosis with an emphasis on unique gastrointestinal toxicities, including toxic megacolon.

Amyloidosis↗
PubMed2000

Diagnosis and treatment of AL amyloidosis.

AL (amyloid light-chain) amyloidosis is a plasma cell disorder in which depositions of amyloid light-chain protein cause progressive organ failure. Virtually all patients with AL amyloidosis have a monoclonal protein in the serum or urine or a monoclonal population of plasma cells in the bone marrow. The most common target organ is the kidney and renal amyloidosis manifests as proteinuria or nephrotic syndrome in 3/4 of the patients. The median survival is one to two years. It is important to recognize that the amyloidosis is a dynamic process, and chemotherapy induced reduction of the activity of the plasma cell clone reduces the supply of the amyloid precursor protein and can result in a major regression of the deposits. Amyloid-related nephrotic syndrome and renal failure are potentially reversible. Conventional-dose melphalan as standard treatment can prolong the median duration of survival about 10 months, but the clinical response rates with improvement of impaired organ function are low with a slow response. Upfront high-dose chemotherapy with autologous peripheral blood stem cell transplantation is much more effective and can result in a major improvement of the patient's clinical condition, but the treatment-related toxicity can be relevant due to impaired organ function. The initial use of a conventional-dose chemotherapy consisting of vincristine, doxorubicin and dexamethasone (VAD) to achieve a remission and subsequent high-dose chemotherapy is the concept of a German trial. The improvement of the condition of the patient by this approach may increase the tolerability of high-dose chemotherapy and reduce transplantation-related problems.

Amyloid↗
PubMedDate not supplied

Primary amyloidosis (AL) as a cause of nephrotic syndrome.

AL amyloidosis is a rare systemic disease resulting from tissue accumulation of amyloid fibrils derived from monoclonal immunoglobulin light chains. It can disrupt the tissue architecture and consequently cause organ dysfunction. The prognosis is poor with a median survival of 13 months in untreated patients. By illustrating the case of a patient whose AL amyloidosis was detected after presenting a nephrotic syndrome, the characteristics of the disease are reviewed as well as diagnostic criteria and current available therapeutics.

Amyloidosis↗
PubMed2001

The V kappa III subgroup light chain proteins in AL amyloidosis & autoimmune diseases.

BACKGROUND & OBJECTIVES: Light chain associated amyloidosis (AL) is characterized by extracellular deposition of immunoglobulin light chain and its fragments. In vitro and in vivo studies have shown that some light chains are nonamyloidogenic and nonnephrotoxic, whereas others are potentially amyloidogenic. Some light chains are prone to be deposited as rheumatoid materials, and also as nodular amorphous aggregates (light chain deposition diseases). These findings suggest that specific sequence element(s) may control the various kinds of light chain associated diseases. In this study we tried to identify such sequence element(s). METHODS: Two Bence Jones proteins (BJPs), NIG93 and NIG2 of subgroup V kappa III, were characterized and compared with other members of the same subgroup whose sequences are available in the data base. RESULTS: Both NIG93 and NIG2 proteins had sequences characteristics of V kappa IIIa as distinguished from V kappa IIIb, subsubgroup proteins. They also contained several novel substitutions, such as Met-37, Leu-40, Val-58, and IIe-85 in NIG93, and Val-2, His-29, Arg-50, and Ile-72 in NIG2. The data accumulated at present indicate that all members of the V kappa IIIa subsubgroup are related to either AL amyloidosis or rheumatoid arthritis, whereas the V kappa IIIb proteins are related to autoimmune diseases. INTERPRETATION & CONCLUSION: These observations indicate that subgroup-specific residues might be critical for light chain pathogenesis, at least for the V kappa III proteins. Point mutations within these proteins may be another structural element controlling their conformation as well as their pathogenic aggregation.

Amino Acid Sequence↗
PubMed1999

What is the role of giant cells in AL-amyloidosis?

AL-amyloidosis is one of the most common amyloidoses and can be found in a localized and a systemic form. The precursor protein is an immunoglobulin light chain which as AL-protein in both localized and systemic AL-amyloidosis shows the same pattern of fragmentation and changes of primary structure. In this work it is shown that that there is a difference between localized and systemic amyloidosis in respect to accompanying giant cells which constantly are found associated with amyloid deposits in localized AL-amyloidosis. In addition, giant cells were found together with amyloid deposits in lymph nodes of some cases of systemic AL-amyloidosis. Based on these findings and electron microscopic studies, it is discussed whether the giant cells actively participate in amyloid fibril formation by uptake and modification of the precursor protein or the giant cells are part of a foreign body reaction. Included in this work are two new cases of localized lung (lambda I) and ureteric (kappa I) AL-amyloidosis.

Amino Acid Sequence↗
PubMed2003

Serum N-terminal pro-brain natriuretic peptide is a sensitive marker of myocardial dysfunction in AL amyloidosis.

BACKGROUND: Brain natriuretic peptide (BNP) is a marker of ventricular dysfunction and can be used to assess prognosis in heart failure and after myocardial infarction. Heart involvement is the most important prognostic factor and causes death in almost all patients with light-chain amyloidosis (AL). We investigated the prognostic value of NT-proBNP and its utility in monitoring amyloid heart dysfunction. METHODS AND RESULTS: NT-proBNP was quantified at diagnosis in 152 consecutive patients seen at the coordinating center of the Italian Amyloidosis Study Group (Pavia) from 1999 throughout 2001. Heart involvement was estimated on the basis of clinical signs, electrocardiography, and echocardiography. NT-proBNP concentrations differed in patients with (n=90, 59%) and without (n=62, 41%) heart involvement (median: 507.8 pmol/L versus 22.1 pmol/L, P=10(-7)). The best cutoff for heart involvement was at 152 pmol/L (sensitivity: 93.33%, specificity: 90.16%, accuracy: 92.05%) and distinguished two groups with different survival (P<0.001). The Cox multivariate model including NT-proBNP was better than models including echocardiographic and clinical signs of heart involvement. NT-proBNP appeared to be more sensitive than conventional echocardiographic parameters in detecting clinical improvement or worsening of amyloid cardiomyopathy during follow-up. CONCLUSIONS: NT-proBNP appeared to be the most sensitive index of myocardial dysfunction and the most powerful prognostic determinant in AL amyloidosis. It adds prognostic information for newly diagnosed patients and can be useful in designing therapeutic strategies and monitoring response. NT-proBNP is a sensitive marker of heart toxicity caused by amyloidogenic light chains.

Adult↗
PubMed1989

Perimembranous-type renal amyloidosis: a peculiar form of AL amyloidosis.

Six cases of perimembranous-type renal amyloidosis were reported. This type of renal amyloidosis was characterized by amyloid deposition predominantly involving the epithelial aspect of the glomerular capillary wall. Florid spicular arrangement was another representative feature. This type of amyloid deposition was found in 8% of autopsy cases of systemic amyloidosis. All cases were categorized as AL amyloidosis and developed the nephrotic syndrome irrespective of the amount of amyloid within the glomeruli. The results obtained suggest that perimembranous-type renal amyloidosis is a peculiar form of AL amyloidosis both in morphology and clinical manifestations. autopsy cases of systemic amyloidosis. All cases were categorized as AL amyloidosis and developed the nephrotic syndrome irrespective of the amount of amyloid within the glomeruli. The results obtained suggest that perimembranous-type renal amyloidosis is a peculiar form of AL amyloidosis both in morphology and clinical manifestations. autopsy cases of systemic amyloidosis. All cases were categorized as AL amyloidosis and developed the nephrotic syndrome irrespective of the amount of amyloid within the glomeruli. The results obtained suggest that perimembranous-type renal amyloidosis is a peculiar form of AL amyloidosis both in morphology and clinical manifestations.

Amyloid↗
PubMed2003

Endothelial dysfunction precedes C-fiber abnormalities in primary (AL) amyloidosis.

Primary (AL; immunoglobulin light-chain associated) amyloidosis is characterized by the deposition of pathological proteins in the extracellular matrix of tissues and organs. Autonomic and sensory peripheral neuropathy is a common feature of this disorder. The pathogenesis of the neuropathy is poorly defined. The aims of this study were to investigate vascular and neural function in the cutaneous microcirculation of AL amyloidosis patients. Seven patients with AL amyloidosis and controls were studied. Acetylcholine and sodium nitroprusside were iontophoresed into the forearm skin. Endothelial, smooth muscle, and C-fiber-mediated cutaneous blood flow (CuBF) were recorded by laser Doppler flowmetry. Endothelial vasodilation in the forearm skin was attenuated in AL amyloidosis patients (p = 0.007). Maximum endothelium-mediated CuBF in the patient group was reduced (p = 0.047). No group differences could be detected in the C-fiber response or smooth muscle vasodilation (p value not significant). Maximum C-fiber and endothelium-independent CuBF did not differ between the two groups (p value not significant). Early in the disease, AL amyloidosis patients present with impaired endothelial function. At this stage, C-fiber and smooth muscle function are still preserved. These data suggest that endothelial abnormalities precede and may contribute to the pathogenesis of the neuropathy associated with AL amyloidosis.

Adult↗
PubMed1992

[Inflammatory cell infiltration around beta 2-microglobulin amyloid deposition: histologic comparison of beta 2-microglobulin amyloidosis with AA or AL amyloidosis].

Thirty-one autopsy cases of beta 2-microglobulin (beta 2M) amyloidosis were pathologically investigated in comparison with 17 autopsy cases of AA or AL amyloidosis. In 20 cases (65%, 20/31) of beta 2M amyloidosis, inflammatory cells, mainly macrophages were seen infiltrating around beta 2M amyloid in intervertebral disks. The more beta 2M amyloidosis advances, the more macrophage infiltration tends to be prominent. In cases of severe beta 2M amyloidosis, the cytoplasm of macrophages around amyloid deposition were swollen with engulfed amyloid substance and were often transforming to foreign body multinucleated giant cells. In addition, granulation tissue was formed with infiltrating macrophages, foreign body multinucleated giant cells, capillary proliferation and fibrosis around beta 2M amyloid deposition. On the other hand, inflammatory cell infiltration around amyloid deposition was scarcely seen in AA or AL amyloidosis. Ultrastructurally, macrophages were abundant in phagocytic vacuoles containing amyloid fibrils. These macrophages were immunohistochemically positive for CD68, IL-1 beta and TNF-alpha. Thus, macrophage infiltration around beta 2M amyloid is thought to be responsible for local pain and tissue destruction of dialysis patients.

Amyloid↗
PubMed1984

Primary (AL) amyloidosis as a cause of breast masses.

Amyloidosis is rarely considered in the differential diagnosis of breast masses. During the past six years, 27 women with primary (24) and multiple myeloma-associated (three) amyloidosis (AL amyloid) were evaluated at our center. In five of these patients, amyloid was demonstrated on microscopic examination of breast tissue. The clinical presentations were similar to fibrocystic breast disease in two cases and malignancy in two others. Amyloidosis of the breast may be more common than previously recognized, especially considering the predilection of amyloid for depositing around fat cells. Therefore, pathologic examination of nonmalignant breast tissue should include Congo red staining and viewing under polarized light.

Amyloid↗